Efficient muco-ciliary clearance is maintained by a multi- regulatory system complex. The prime objective of the proposed work is to elucidate the fundamental organization and behaviour characteristics of the regulatory system complex by a comprehensive approach. Further refinement of the model of muco-ciliary clearance and development of the basis for a rational approach to prevention and treatment of chronic lung diseases related to environmental noxious agents is our ultimate goal. The response of the muco-ciliary clearance system to a variety of therapeutic and environmental agents will be evaluated by simultaneous in vivo and in vitro measurements of mucus flow volume, mucus flow velocity, ciliary beat rates, and rheological and chemical properties of respiratory mucus secretions. The results obtained will be carefully analyzed to identify the primary site and mode of action of the agents applied. In addition, a possible interaction between the individual components of the regulatory system complex will be evaluated by applying two agents simultaneously. Similarly the possible preventive value of therapeutic agents will be evaluated by applying a variety of therapeutic agents simultaneously with the application of noxious environmental agents. In complementing these physiological studies, cooperative chemical studies will be carried out to identify and characterize the chemical structure of the major components of the mucus secretion obtained from tracheal pouch preparations. In addition, an attempt will be made to develop a simplified micro-technique for the evaluation of mucin, protein, and electrolyte profiles of mucus secretion. By correlating the rheological and chemical properties of mucus under a variety of experimental conditions the chemical basis for the alteration of rheological properties will be elucidated. Finally, under close cooperation and interactions among physiologist, rheologist, and biochemist, information gathered by the experiments will be integrated into a model of muco-ciliary clearance.